Zinc modulation of insulin-like growth factor's effect in osteoblastic MC3T3-E1 cells

Peptides. 1995;16(6):1063-8. doi: 10.1016/0196-9781(95)00067-t.


Whether the anabolic effect of insulin-like growth factor-I (IGF-I) in osteoblastic MC3T3-E1 cells is modulated by zinc, an activator of bone formation, was investigated in vitro. After subculture for 3 days, the cells were cultured for 72 h with IGF-I (10(-8) M). The peptide produced a significant increase of protein concentration, deoxyribonucleic acid (DNA) content, and cell number in the cells. These increases were markedly enhanced by the presence of zinc sulfate (10(-5) M), but not zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-5) M). Also, the cellular alkaline phosphatase activity was synergistically increased by the presence of both IGF-I and zinc sulfate. Thus, effect was not seen in the presence of both insulin (10(-8) M) and zinc sulfate (10(-5) M). The effect of zinc sulfate to enhance the IGF-I-increased alkaline phosphatase activity and protein concentration in the cells was clearly prevented by the presence of cycloheximide (10(-6) M), staurosporin (10(-8) M), or okadaic acid (10(-7) M) with an effective concentration. However, staurosporin had a partial inhibiting effect on the IGF-I or the IGF-I plus zinc-induced increases in cellular protein, although okadaic acid entirely blocked the IGF-I or the IGF-I plus zinc effect. The present study demonstrates that the anabolic effect of IGF-I in osteoblastic cells is enhanced by zinc ion. The enhancement by zinc may be mediated through the signaling pathway of protein kinase C and protein phosphatase in the cells.

MeSH terms

  • 3T3 Cells
  • Alkaline Phosphatase / metabolism
  • Alkaloids / pharmacology
  • Animals
  • Carnosine / analogs & derivatives
  • Carnosine / pharmacology
  • Cycloheximide / pharmacology
  • DNA / metabolism
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Ethers, Cyclic / pharmacology
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Okadaic Acid
  • Organometallic Compounds / pharmacology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • Proteins / metabolism
  • Staurosporine
  • Zinc / administration & dosage
  • Zinc / pharmacology*
  • Zinc Compounds


  • Alkaloids
  • Enzyme Inhibitors
  • Ethers, Cyclic
  • Insulin
  • Organometallic Compounds
  • Protein Synthesis Inhibitors
  • Proteins
  • Zinc Compounds
  • polaprezinc
  • Okadaic Acid
  • Insulin-Like Growth Factor I
  • Carnosine
  • DNA
  • Cycloheximide
  • Alkaline Phosphatase
  • Staurosporine
  • Zinc